Enhanced establishment of a virus carrier state in adult CD4⁺ T-cell-dencient mice

CD4⁺ T cells play an important role in regulating the immune response; their contribution to virus clearance is variable. Mice that lack CD4⁺ T cells (CD4^-/- mice) and are therefore unable to produce neutralizing antibodies cleared viscero-lymphotropic lymphocytic choriomeningitis virus (LCMV) strain WE when infected intravenously with a low dose (2 × 10² PFU) because of an effective CD8⁺ cytotoxic T-cell (CTL) response. In contrast, infection with a high dose (2 × 10⁶ PFU) of LCMV strain WE led to expansion of antiviral CTL, which disappeared in CD4^-/- mice; in contrast, CD4⁺ T-cell-competent mice developed antiviral memory CTL. This exhaustion of specific CTL caused viral persistence in CD4^-/- mice, whereas CD4⁺ T-cell-competent mice eliminated the virus. After infection of CD4^-/- mice with the faster-replicating LCMV strain DOCILE, abrogation of CTL response and establishment of viral persistence developed after infection with a low dose (5 × 10² PFU), i.e., an about 100-fold lower dose than in CD4⁺-competent control mice. These results show that absence of T help enhances establishment of an LCMV carrier state in selected situations.